1. Field of the Invention
The present invention relates to a microscope system, a specimen observation method, and a computer program product for acquiring a specimen image obtained by capturing the image of the specimen using a microscope and observing the specimen by displaying the acquired specimen image.
2. Description of the Related Art
For example, in a pathological diagnosis, it is widely performed that a tissue sample obtained by organ harvesting or needle biopsy is thinly sliced to a thickness of several microns to create a specimen, and the specimen is magnified and observed by using an optical microscope to obtain various findings. Here, the specimen hardly absorbs or scatters light and is nearly clear and colorless, so that it is generally stained by dye before the observation.
Various types of staining methods are proposed. In particular, for a tissue specimen, as morphological observation staining for observing morphology of the specimen, hematoxylin-eosin staining (hereinafter referred to as “HE staining”) that uses two types of dyes, hematoxylin and eosin, is normally used. For example, a method is disclosed in which an image of an HE-stained specimen is captured by multiband imaging, an amount of dye that stains the specimen is calculated (estimated) by estimating a spectrum at a specimen position, and an RGB image to be displayed is synthesized (for example, refer to Japanese Laid-open Patent Publication No. 2008-51654, Japanese Laid-open Patent Publication No. 07-120324, Japanese National Publication of International Patent Application No. 2002-521682, or the like). As another morphological observation staining, for example, in cytological diagnosis, Papanicolaou staining (Pap staining) is known.
In a pathological diagnosis, molecule target staining to check an expression of molecule information is performed on a specimen to be used for diagnosis of function abnormality, such as expression abnormality of a gene or a protein. For example, the specimen is fluorescently labeled using an IHC (immunohistochemistry) method, an ICC (immunocytochemistry) method, and an ISH (in situ hybridization) method and fluorescently observed, or is enzyme-labeled and observed in a bright field. In this case, in the fluorescent observation of the specimen by the fluorescent labeling, for example, a confocal laser microscope is used. In this observation by the fluorescent labeling, a highly-sensitive and sharp image can be acquired, and the specimen can be three-dimensionally observed or the specimen can be observed from a desired direction. Also, there is an advantage that a plurality of target molecules can be labeled at the same time. However, there is a problem that the observation by the fluorescent labeling cannot be performed easily because the specimen cannot be preserved for a long period of time, the diagnosis takes a long time, and a dedicated dark room is required. In addition, there is also a problem that the observation by the fluorescent labeling is difficult to be performed at the same time as the morphological observation of the specimen, so that the observation by the fluorescent labeling is not so practical in the pathological diagnosis.
Meanwhile, in the bright field observation by the enzyme-labeling (the IHC method, the ICC method, and the CISH method), the specimen can be semi-permanently preserved. Since an optical microscope is used, the observation can be performed together with the morphological observation, and is used as the standard in the pathological diagnosis.
On the other hand, in recent years, as a medical treatment for cancer or the like, a medical treatment called molecular target treatment that uses a therapeutic drug (antibody therapeutic drug) acting on a specific molecular target is performed, and therapeutic effects and side-effect-reducing effects are expected. For example, in the cancer treatment by the molecular target treatment, an antibody therapeutic drug targeting molecules (antigenic proteins) specific to cancer cells is used. Drugs that are allowed to be used as the antibody therapeutic drug include, for example, Trastuzumab (Herceptin (registered trademark)) that is an anti-HER2 antibody drug against breast cancer, and Cetuximab (Erbitax (registered trademark)) that is an anti-EGFR antibody drug against large intestine cancer.
In diagnosis of cancer, for example, whether or not an antigen (target molecule) that is a target molecule of the antibody therapeutic drug is expressed on the surface of a cell or a cell membrane is observed by the IHC method or the like, and suitable patients are selected.
Or, antibodies against a plurality of antigens are applied to label each antigen, and the combination of presences and absences of the expressions of the antigens is evaluated (antigen panel evaluation). For example, a cancer stem cell is identified by evaluating a combination of antigens expressed on a cell membrane. As a specific example, in diagnosis of breast cancer, a cell in which CD44 molecule is expressed on the cell membrane and CD24 molecule is not expressed (or expression rate of the CD24 molecule is low) on the cell membrane is identified as the cancer stem cell. On the other hand, in diagnosis of large intestine cancer, a cell in which CD44 molecule and CD133 molecule are expressed on the cell membrane is identified as the cancer stem cell. Further, various antibody panel evaluations such as estimation of a primary site of a cancer of unknown primary site (for example, differentiation of large intestine cancer, breast cancer, and lung epithelial cancer), differentiation of B-cell lymphoma and T-cell lymphoma, identification of mesothelioma, and differentiation of squamous cell cancer and adenocarcinoma are performed by applying antibodies for an intended purpose to label antigens.